Atherosclerosis is a cardiovascular condition occurring as a result of narrowing down of the arterial walls. The narrowing is due to the formation of plaques (raised patches) or streaks in the inner lining of the arteries. These plaques consist of foam cells of low-density lipoproteins, oxidized-LDL, decaying muscle cells, fibrous tissue, clumps of blood platelets, cholesterol, and sometimes calcium. They tend to form in regions of turbulent blood flow and are found most often in people with high concentrations of cholesterol in the bloodstream. The number and thickness of plaques increase with age, causing loss of the smooth lining of the blood vessels and encouraging the formation of thrombi (blood clots). Sometimes fragments of thrombi break off and form emboli, which travel through the bloodstream and block smaller vessels.
The blood supply is restricted to the heart, eventually forming a blood clot leading to death. The major causes of atherosclerosis are hypercholesterolemia and hyperlipidemia is high circulating cholesterol and high lipids like LDL-cholesterol and triglycerides in the blood. These lipids are deposited in the arterial walls, obstructing the blood flow and forming atherosclerotic plaques leading to death.
Atherosclerosis is responsible for more deaths in countries, such as in the Unites States of America, than any other single condition. Atherosclerotic heart  disease involving the coronary arteries is the most common single cause of death, accounting for one third of all deaths. Atherosclerotic interference with blood supply to the brain (causing stroke) is the third most common cause of death after cancer. Atherosclerosis also causes a great deal of serious illness by reducing the blood flow in other major arteries, such as those to the kidneys, the legs and the intestines.
Medication is not a satisfactory treatment because much of the damage to the artery walls has already been done. Anticoagulant drugs have been used to try to minimize secondary clotting and embolus formation, but have little or no effect on the progress of the disease. Vasodilator drugs are used to provide symptom relief, but are of no curative value.
Surgical treatment is available for certain high-risk situations. Balloon angioplasty can open up narrowed vessels and promote an unproved blood supply. The blood supply to the heart muscle can also be restored through a vein graft bypass. Large atheromatous and calcified arterial obstructions can be removed by endarterectomy, and entire segments of diseased peripheral vessels can be replaced by woven plastic tube grafts.
There is a need for a new therapy, possibly to prevent these conditions and insure better health, particularly in people who are genetically predisposed to such conditions. The present invention fulfills these and other needs.
There is now accumulating evidence for a novel functionally distinct subpopulation of T cells, called regulatory T cells that exert important regulatory functions in various immuno-inflammatory diseases (see references 12 to 14 for review). Several subsets of regulatory T (Tr) cells with distinct phenotypes and distinct mechanisms of action have now been identified. These include Tr1 cells (15 to 20), which secrete high levels of interleukin (IL)-10 and low to moderate levels of transforming growth factor (TGF)-β, Th3 cells (21,22), which primarily secrete TGF-β, and CD4+CD25+ T cells, which inhibit immune responses through cell-cell contact (23). We have shown that  repeated stimulation of naive T cells, from OVA T-cell receptor (TCR)-transgenic mice with OVA and IL-10, results in the generation of T-cell clones with a unique cytokine profile distinct from that of Th0, Th1 or Th2 cells (15). These Tr1 cells produce IL-10, IL-5 and IFN-γ, with or without TGF-β, but with little or no IL-2 or IL-4, and proliferate poorly following polyclonal TCR-mediated activation. Functional studies have shown that Tr1 cells have immunosuppressive properties and have been shown to prevent the development of Th1-mediated autoimmune diseases (15). Co-culture of naïve CD4+ T cells and human Tr1 clones in the presence of allogenic antigen-presenting cells (APCs) results in the suppression of proliferative responses (15). Similarly, Tr1 clones specific for filamentous haemaggultinin (HA) from Bordetella pertussis suppress proliferation and cytokine production by a Th1 clone against an unrelated antigen, influenza virus HA (20). In both cases, the suppressive effects of Tr1-cell clones are reversed by neutralizing IL-10, suggesting that, regardless of their antigen specificities, Tr1 cell suppression is a bystander effect mediated through the production of IL-10.
Here, we tested whether transfer of Tr1 cells in mammals could reduce immune inflammatory processes and more specifically could reduce risk of artherosclerosis. We show for the first time that transfer of such Tr1 cells to apoE knockout (KO) mice inhibits pathogenic Th responses and reduces the development of atherosclerosis.